Int Rev Neurobiol
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Stroke is a major risk factor for developing acquired epilepsy (AE). Although the underlying mechanisms of ischemia-induced epileptogenesis are not well understood, glutamate has been found to be associated with both epileptogenesis and ischemia-induced injury in several research models. This chapter discusses the development of an in vitro model of epileptogenesis induced by glutamate injury in hippocampal neurons, as found in a clinical stroke, and the implementation of this model of stroke-induced AE to evaluate calcium's role in the induction and maintenance of epileptogenesis. ⋯ The permanent epileptiform phenotype expressed as SREDs that resulted from glutamate injury was found to be dependent on the presence of extracellular calcium. The "epileptic" neurons manifested elevated intracellular calcium levels when compared to control neurons, independent of neuronal activity and seizure discharge, demonstrating that alterations in calcium homeostatic mechanisms occur in association with stroke-induced epilepsy. Findings from this investigation present the first in vitro model of glutamate injury-induced epileptogenesis that may help elucidate some of the mechanisms that underlie stroke-induced epilepsy.
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Pain is a common problem of patients with multiple sclerosis (MS) and may be due to central/neuropathic or peripheral/somatic pathology. Rarely MS may present with pain, or pain may herald an MS exacerbation, such as in painful tonic spasms or Lhermitte's sign. In other patients, pain may become chronic as a long-term sequela of damage to nerve root entry zones (trigeminal neuralgia) or structures in central sensory pathways. ⋯ The pathophysiology of pain in MS may be linked to certain plaque locations which disrupt the spinothalamic and quintothalamic pathways, abnormal impulses through motor axons, development of an acquired channelopathy in affected nerves, or involve glial cell inflammatory immune mechanisms. At this time, the treatment of pain in MS employs the use of antiepileptic drugs, muscle relaxers/antispasmodic agents, anti-inflammatory drugs, and nonpharmacological measures. Research concerning cannabis-based treatments shows promising results, and substances which block microglial or astrocytic involvement in pain processing are also under investigation.
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Status epilepticus (SE) is a medical and neurological emergency requiring prompt and aggressive treatment, particularly for elderly individuals in whom comorbid conditions may increase the severity of consequences in SE. Generalized convulsive status epilepticus (GCSE) is the most common and life-threatening type of SE. It may be overt or subtle in its presentation. ⋯ Analysis of data on elderly patients with overt GCSE from a Veterans Affairs cooperative study revealed that success rates of first-line treatment were 71.4% for phenobarbital, 63.0% for lorazepam, 53.3% for diazepam followed by phenytoin, and 41.5% for phenytoin alone. In elderly patients with subtle GCSE, success rates for first-line treatment were 30.8% for phenobarbital, 14.3% for lorazepam, 11.8% for phenytoin, and 5.6% for diazepam followed by phenytoin. Because each drug has advantages and disadvantages, the choice of which agent to use as first-line treatment depends on individual patient characteristics.
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The knowledge base for treating elderly persons with epilepsy is limited. There are few known knowns, many known unknowns, and probably many unknown knowns, that is, the things we know that "ain't so." We know that the incidence and prevalence of epilepsy is higher in the elderly than any other age group, that the elderly are not a homogeneous group, that epilepsy is much more common in the nursing home population than in the community-dwelling elderly, and that antiepileptic drug (AED) use varies greatly among countries, but that in all, the older AEDs (phenytoin, phenobarbital, and carbamazepine) are the most commonly used. ⋯ Some unknown knowns (i.e., misconceptions) are that the elderly need levels of AEDs similar to those for younger adults and that AED levels do not fluctuate widely. This book is designed to help the reader understand the issues and, hopefully, to stimulate research to provide answers for the known unknowns.
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Understanding the importance of cortical lesions in MS pathogenesis has changed. Histopathologic studies using new immunohistochemical methods show that cortical lesions can be detected more frequently than previously reported. Newer MRI sequences also detect cortical lesions more accurately. ⋯ We observed a significant correlation between T2-LV and GM atrophy in all slice thickness (r = -0.4 to -0.48, p = 0.001-0.003) and a modest relationship between cortical and cortical-juxtacortical LVs and disability, especially at 1.5-mm slice thickness (r = 0.35, p = 0.025). Use of thinner slices (1.5 mm) on 2D-FLAIR images can significantly increase the sensitivity and precision of detecting cortical and juxtracotical lesions in patients with MS. Cortical and juxtacortical lesions contribute more to disability development than total T2-LV alone.